Exploring the functional role of XIST in breast cancer from mechanisms to clinical implications

Abstract

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in cancer biology, with the X-inactive specific transcript (XIST) playing a particularly significant role in breast cancer development and progression. This review summarizes current insights into XIST's mechanistic roles, highlighting its involvement in intricate regulatory networks through interactions with microRNAs, transcription factors, and key signaling pathways. Furthermore, we explore its significant influence on critical aspects of tumor progression, including chemotherapy resistance, modulation of the tumor microenvironment, and regulation of cancer stem cells. Importantly, emerging evidence indicates that XIST functions are not uniform across breast cancer subtypes; rather, its expression patterns and biological effects appear to be context-dependent, varying between luminal and triple-negative breast cancer (TNBC) categories. While XIST is frequently associated with tumor-promoting activities, certain subtype-specific contexts suggest a more complex regulatory role, underscoring the need for stratified interpretation. By bridging mechanistic insights with clinical applications, we demonstrate XIST's considerable promise as a diagnostic and prognostic biomarker and as a novel therapeutic target. In this review, we demonstrate that targeting XIST may offer a novel and effective therapeutic avenue, contributing to personalized treatment strategies and improved outcomes in breast cancer.